Transposition is a genetic rearrangement process in which DNA sequences termed transposable elements "move" from one DNA location to another. A molecular understanding of transposition is important because: similar DNA rearrangements are likely to have played an important role in genome evolution and in the somatic cell chromosome changes associated with some cancer, retrovirus genome integrate into host chromosomes by a transposition like process, and bacterial transposable elements frequently carry (and help disseminate) antibiotic resistant genes. Furthermore, these studies will elucidate how a single polypeptide, the Tn5 transposase, is able to perform the multiple sequential functions involved in transposition. The investigator will use the bacterial transposon Tn5 to study the molecular basis for transposition. The studies will involve: X-ray crystallographic structural analyses of transposase and transposase domains and DNA sequences involved in various transposition steps (transposase/DNA end sequence binding, synaptic complex formation, DNA cleavage, target capture, and DNA strand transfer). Because of the progress made to date in their structural, genetic and biochemical studies, this is a potentially rewarding time in the study of Tn5 transposition.